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Biomedical subjects

J J Legros

Publications and source records attributed to J J Legros.

At least 109 records · Page 6Linked to original sources

The neurohormonal thymic microenvironment: immunocytochemical evidence that thymic nurse cells are neuroendocrine cells.

Thymic neuroendocrine cells were identified by immunofluorescence in the murine thymus through the use of monoclonal antibody A2B5, and specific polyclonal antisera against neurophysin (NP), oxytocin (OT) and arginine vasopressin (AVP). Two reactive regions were clearly identified: the subcapsular cortex and the medulla. A close correspondence was observed between A2B5-reactive and NP-immunoreactive cells in the medulla. An important epithelial population of the subcapsular cortex, the thymic nurse cells (TNCs), were found to be A2B5-positive and to contain immunoreactive NP, OT and AVP. The neuroendocrine nature of TNCs was further substantiated by their high reactivity with an antiserum against neuron-specific enolase. These observations demonstrate the presence in the thymus gland of an original neuroendocrine microenvironment which could be of functional importance in the mediation of central influences upon T lymphocyte differentiation.

Animals↗

Inhibitory action of exogenous oxytocin on plasma cortisol in normal human subjects: evidence of action at the adrenal level.

In previous studies we demonstrated that exogenous oxytocin induces a decrease of basal and stimulated cortisol and ACTH plasma levels in the normal male. To rule out the possibility that oxytocin could also act at the adrenal level, we tested, in the present work, the influence of exogenous oxytocin on the cortisol increase secondary to the intravenous injection of a supraphysiological dose (0.25 mg) of synthetic ACTH1-24 (Synachten) in 9 normal male volunteers. We demonstrate that oxytocin infusion does not modify the ACTH plasma levels but, however, induces a decreased cortisol response to ACTH1-24. These results support the hypothesis that, beside its hypophysial inhibitory action on ACTH release, oxytocin acts also at the adrenal gland level to decrease cortisol release and/or synthesis in normal human subjects.

Adrenal Glands↗

Blunted response of growth hormone to clonidine and apomorphine in endogenous depression.

We measured the growth hormone (GH) response to clonidine (an alpha-2-adrenergic agonist) and to apomorphine (a dopaminergic agonist) in 15 major endogenous and 15 minor depressive in-patients matched for gender and age. Results showed a significantly smaller GH response in the major depressives to both clonidine (P less than 0.01) and apomorphine (P less than 0.001). No significant difference existed between the two groups with regard to changes in blood pressure and pulse rate during either test. While major depressives showed a trend toward smaller sedative side-effects than minor depressives after clonidine, they showed significantly smaller sedative and gastro-intestinal side-effects after apomorphine. No significant correlation was present either in the major depressive or in the minor depressive group between the GH responses following clonidine and apomorphine challenges. These results support the hypothesis of both noradrenergic and dopaminergic neurotransmitter disturbances in major depression, with individual variability with regard to those biochemical anomalies.

Adult↗

Identification of vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate secretion of antidiuretic hormone and an oat cell carcinoma.

In this study we have identified and characterized several vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion and oat cell carcinoma of the lung. Immunoreactive plasma vasopressin was measured after gel filtration (Sephadex G-25) or C-18 cartridge extraction using two different region-specific antisera: AS1 and AS2. Antiserum AS1 is more specifically directed towards the antigenic site of the hexapeptidic ring of arginine-vasopressin (AVP), whereas AS2 is more specifically directed towards the C-terminal region of AVP. Unexpectedly, the Sephadex G-25 gel filtration elution profile of the immunoreactive vasopressin was very heterogeneous, indicating the presence of several molecular species. After extraction of total AVP and AVP-like peptides of this plasma, an unusual AS1/AS2 ratio of immunoreactivity was observed, suggesting the presence of vasopressin-like peptides which differ from AVP in the C-terminus.

Aged↗

Diagnostic performance of basal free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) ratio in endogenous depression: comparison with the dexamethasone suppression test.

We assessed the 8:00 AM ratio of free cortisol/18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in 56 endogenous depressive inpatients and in 22 normal volunteers. A ratio higher than 40 was associated with a diagnostic sensitivity for endogenous depression of 75%, a specificity of 95.5%, and a diagnostic confidence of 97.7%. These diagnostic results were at least equivalent to the Dexamethasone Suppression Test (DST) using a cortisol cut-off limit of 5 micrograms/dl. This may thus represent a simpler procedure than the DST in the diagnostic analysis of endogenous depression.

18-Hydroxydesoxycorticosterone↗

Neuroendocrine evaluation of catecholaminergic neurotransmission in mania.

Several lines of evidence suggest catecholamine overactivity (noradrenergic and/or dopaminergic) in mania. We studied the growth hormone (GH) response to clonidine (an alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) in seven inpatients meeting Research Diagnostic Criteria for mania. They had been completely drug free for at least 3 months before the neuroendocrine procedures and were age- and sex-matched to seven major depressive and seven minor depressive inpatients, drug free for at least 2 weeks. GH was assayed every 20 min for 40 min before and 120 min after either clonidine (0.15 mg i.v.) or apomorphine (0.5 mg s.c.), with an interval of at least 2 days between the tests. The three groups differed significantly in the GH peak response: after clonidine (mean +/- SD), 3.2 +/- 2.4 ng/ml in manics, 3.2 +/- 2.4 ng/ml in major depressives, and 13.2 +/- 8.7 ng/ml in minor depressives; after apomorphine, 10.5 +/- 7.4, 3.2 +/- 1.9, and 26.9 +/- 15.8, respectively. While there were significant differences between manics and minor depressives and between major and minor depressives after both clonidine and apomorphine, manics did not significantly differ from major depressives on either test. These results do not provide neuroendocrine support to the catecholaminergic hypothesis of manic disorders.

Adult↗

Intranasal oxytocin in obsessive-compulsive disorder.

A 55-year patient with obsessive-compulsive disorder showed clear improvement during 4 weeks of treatment with intranasal oxytocin compared to 4 weeks of intranasal placebo. This improvement was concurrent with the development of severe memory disturbances, supporting the amnestic properties of the peptide. However, the patient also developed psychotic symptoms and a marked decrease in plasma sodium and osmolality, which may have masked the obsessive symptomatology. This case highlights the need for careful monitoring in long-term oxytocin therapy.

Administration, Intranasal↗

Confirmation of the inhibitory influence of exogenous oxytocin on cortisol and ACTH in man: evidence of reproducibility.

The influence of low-dose oxytocin perfusion (32 mIU/min) on ACTH and cortisol plasma levels was tested in 8 normal male volunteers (age 18-26). The 1-h oxytocin perfusion periods were preceded and followed by two 1-h saline control periods. During the first period, there was a slight ACTH concentration decrease in 4 individuals. Oxytocin perfusion induced a clear-cut plasma ACTH decrease in 7 out of the volunteers, and a slight decrease in the remaining one. During the second saline infusion, there was a marked ACTH increase in 7 out of the volunteers, and a weak increase in one (P less than 0.0001). A similar pattern was observed in the plasma cortisol levels (P less than 0.00001). Furthermore, a control saline perfusion was performed in 4 of the 8 volunteers and compared to the 4 corresponding oxytocin perfusion tests: the differences between the 2 sets of tests was highly significant both for ACTH (P less than 0.003) and for cortisol (P less than 0.007). Lastly, the reproducibility of this inhibitory influence was retested in 4 volunteers: the tests were repeated under the same conditions 7 days later. There were no global differences between the 2 sets of tests either for ACTH (NS) or for cortisol (NS). ACTH and cortisol concentration fluctuations during the period between each set of tests were not significant. The following variations were measured for ACTH (NS) and for cortisol (NS). The present results confirm the inhibitory influence of low-dose oxytocin perfusion on ACTH and cortisol levels in normal males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus.

Immunoreactive oxytocin and neurophysin were identified and measured by radioimmunoassay in human thymus extracts. Serial dilutions of extracts paralleled the appropriate standard curves. Thymus-extracted oxytocin and neurophysin eluted in the same positions as reference preparations on Sephadex G-75. Authenticity of oxytocin was confirmed by biological assay and high-performance liquid chromatography analysis. In most instances, thymus contents of oxytocin and neurophysin were far greater than those expected from known circulating concentrations and declined with increasing age. The molar ratio of oxytocin to neurophysin in thymus was similar to that found in the hypothalamo-neurohypophyseal system, which strongly suggested with the other data a local synthesis of oxytocin. These findings indicate the presence of neurohypophyseal peptides in the human thymus and further support the concept of a neuroendocrine function integrated in an immune structure.

Adult↗

Are opioid peptides co-localized with vasopressin or oxytocin in the neural lobe of the rat?

The content of vasopressin, oxytocin, neurophysin, leucine-enkephalin, methionine-enkephalin, dynorphin-(1-13), and alpha-neoendorphin in the rat neurohypophysis was measured after different periods of dehydration and after depolarisation of isolated neural lobes and of neurosecretory nerve endings. The rates at which the amount of neurohypophysial hormone and opioid peptides decreased, and the changes in the ratios between the amount of vasopressin or oxytocin and opioid peptide in the neurohypophysis after dehydration and in the incubation medium after depolarization in vitro cast some doubt on, and can be explained by mechanisms other than co-localisation of the different peptides.

Animals↗

Plasma vasopressin, neurophysin, renin and aldosterone during a 4-day head-down bed rest with and without exercise.

The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.

Adult↗

Dexamethasone suppression test and MMPI scales.

In 42 major depressive inpatients, we analyzed the relationship between dexamethasone suppression test (DST) results and Minnesota Multiphasic Personality Inventory (MMPI) scales. Cortisol levels following DST were positively correlated with the depression as well as the social introversion MMPI scale scores, and negatively correlated with the hypomania scale scores. DST nonsuppressor depressives (n = 15) exhibited significantly higher scores on the social introversion scale and significantly lower scores on the hypomania subscale than DST suppressors (n = 27). Moreover, stepwise discriminant analysis using the hypomania score was able to correctly classify 71% of the sample according to DST dichotomy, whereas the association of other scales did not significantly improve the classification. Therefore, these results support a relationship between DST and depressive/manic psychopathology rather than anxious psychopathology.

Adolescent↗

Effect of swim training on systolic blood pressure, vasopressin and total neurophysins in the Lyon hypertensive rat.

This study reports the effects of 5 weeks of swim training on systolic blood pressure, body weight, plasma and brain vasopressin and total neurophysins in the Lyon genetically hypertensive (LH) rat and in their normotensive (LN) and low blood pressure (LL) controls. Swimming was unable to influence any studied parameters. These results shed doubt on the efficiency of this model of training on the evolution of hypertension in the LH rats.

Animals↗